WO1999056772A2 - Hepatitis vaccine - Google Patents
Hepatitis vaccine Download PDFInfo
- Publication number
- WO1999056772A2 WO1999056772A2 PCT/EP1999/003024 EP9903024W WO9956772A2 WO 1999056772 A2 WO1999056772 A2 WO 1999056772A2 EP 9903024 W EP9903024 W EP 9903024W WO 9956772 A2 WO9956772 A2 WO 9956772A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vaccine composition
- hepatitis
- formol
- dose
- aluminium
- Prior art date
Links
- 229960002520 hepatitis vaccine Drugs 0.000 title 1
- 229960005486 vaccine Drugs 0.000 claims abstract description 58
- 239000000203 mixture Substances 0.000 claims abstract description 53
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 39
- 229960004279 formaldehyde Drugs 0.000 claims abstract description 35
- 235000019256 formaldehyde Nutrition 0.000 claims abstract description 35
- 208000002672 hepatitis B Diseases 0.000 claims abstract description 25
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 21
- 241000709721 Hepatovirus A Species 0.000 claims abstract description 20
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims abstract description 18
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims abstract description 17
- 229910021502 aluminium hydroxide Inorganic materials 0.000 claims abstract description 17
- 229940001007 aluminium phosphate Drugs 0.000 claims abstract description 17
- 208000005252 hepatitis A Diseases 0.000 claims abstract description 14
- 238000009472 formulation Methods 0.000 claims abstract description 13
- 239000000427 antigen Substances 0.000 claims description 24
- 102000036639 antigens Human genes 0.000 claims description 24
- 108091007433 antigens Proteins 0.000 claims description 24
- 159000000013 aluminium salts Chemical class 0.000 claims description 11
- 229910000329 aluminium sulfate Inorganic materials 0.000 claims description 11
- 101710137302 Surface antigen S Proteins 0.000 claims description 4
- 101000874347 Streptococcus agalactiae IgA FC receptor Proteins 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 description 9
- 229940124922 Twinrix Drugs 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 125000003275 alpha amino acid group Chemical group 0.000 description 4
- 229960000074 biopharmaceutical Drugs 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 229940124914 Havrix Drugs 0.000 description 3
- 102100031673 Corneodesmosin Human genes 0.000 description 2
- 229940124884 Engerix-B Drugs 0.000 description 2
- 101001065501 Escherichia phage MS2 Lysis protein Proteins 0.000 description 2
- LUTSRLYCMSCGCS-BWOMAWGNSA-N [(3s,8r,9s,10r,13s)-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,16-decahydrocyclopenta[a]phenanthren-3-yl] acetate Chemical compound C([C@@H]12)C[C@]3(C)C(=O)CC=C3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)C)C1 LUTSRLYCMSCGCS-BWOMAWGNSA-N 0.000 description 2
- 239000013065 commercial product Substances 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000000405 serological effect Effects 0.000 description 2
- 101710139375 Corneodesmosin Proteins 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 229940001442 combination vaccine Drugs 0.000 description 1
- 239000011246 composite particle Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002480 immunoprotective effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/29—Hepatitis virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/125—Picornaviridae, e.g. calicivirus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/29—Hepatitis virus
- A61K39/292—Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5252—Virus inactivated (killed)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/70—Multivalent vaccine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/32011—Picornaviridae
- C12N2770/32411—Hepatovirus, i.e. hepatitis A virus
- C12N2770/32434—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- Vaccines for the prophylaxis of hepatitis A and hepatitis B infections are well known.
- the vaccine Engerix-B (Trade Mark) from SmithKline Beecham Biologicals is used to prevent Hepatitis B.
- This vaccine comprises hepatitis B surface antigen (specifically the 226 amino acid S- antigen described in Harford et al. in Postgraduate Medical Journal, 1987, 63 (Suppl. 2), 65-70) and is formulated using aluminium hydroxide as adjuvant.
- the vaccine Havrix also from SmithKline Beecham Biologicals can be used to prevent hepatitis A infections and is also formulated with aluminium hydroxide as adjuvant.
- This vaccine comprises an attenuated strain of the HM-175 Hepatitis A virus inactivated with formol (formaldehyde); see Andre et al [Prog Med. Virol. 1990, vol 37; p72-95].
- the vaccine Twinrix (Trade Mark) which is a combination of the above hepatitis A and hepatitis B antigens may be used to protect against hepatitis A and hepatitis B simultaneously.
- European patent 0 339 667 (Chemo Sero) describes the general concept of combining a hepatitis A antigen and a hepatitis B antigen to make a combination vaccine.
- the adjuvant which is used is not critical: it must only be capable of enhancing the immune activity to a desired extent and not cause any side- effects.
- aluminium gel may be used, in particular aluminium hydroxide gel and aluminium phosphate gel.
- PCT application WO 93/24148 (SmithKline Beecham) describes the preparation of vaccines comprising hepatitis B surface antigen in which aluminium phosphate is used as adjuvant. Multivalent combination vaccines which may optionally contain a hepatitis A antigen, are described. The use of formol is not disclosed.
- European Patent Number 0 633 784 (SmithKline Beecham) describes novel vaccine formulations comprising a hepatitis B component, particularly hepatitis B surface antigen, in combination with aluminium phosphate, and 3 de-O-acylated monophosphoryl lipid A. It has now been surprisingly found that vaccines comprising hepatitis B and/or hepatitis A antigens give exceptionally good results if the vaccine is formulated in a specific manner.
- vaccine formulations according to the invention it is possible to administer the vaccines in a 2 dose, rather than a 3 dose, regimen.
- an aqueous vaccine composition comprising hepatitis B surface antigen which is formulated with aluminium phosphate as adjuvant, the concentration of aluminium phosphate being selected such that there is a ratio of 0.015-0.1 mg aluminium phosphate per ug hepatitis B surface antigen.
- the ratio is in the range 0.02 to 0.08mg aluminium phosphate per ⁇ g HBsAg.
- an inactivated hepatitis A virus may optionally be added to the formulation of the invention, providing a combined hepatitis A plus B vaccine which may be administered in a 2 dose schedule.
- HAV hepatitis A virus
- the hepatitis A antigen is preferably the HM-175 strain used in the commercial product Havrix (SmithKline Beecham Biologicals).
- the concentration of hepatitis A antigen in the vaccine formulation of the invention is preferably about 720-2880 EU units per ml.
- EU units see Andre et al (1990) loc cit.
- compositions of the invention which comprise HAV may additionally comprise aluminium hydroxide, the total amount of aluminium hydroxide generally being 0.05- 0.10 mg per ml.
- the total amount of aluminium salt per 0.5 or 1 ml dose is normally in the range 0.4- l .Omg.
- formol formaldehyde
- the formol concentration is about 20-160 ⁇ g per ml.
- hepatitis B antigen will be hepatitis B surface antigen (HBsAg).
- HBsAg hepatitis B surface antigen
- the preparation of Hepatitis B surface antigen (HBsAg) is well documented. See for example, Harford et al in Develop. Biol. Standard 54, page 125 (1983), Gregg et al in Biotechnology, 5, page 479 (1987), EP-A- 0 226 846, EP-A-0 299 108 and references therein.
- Hepatitis B surface antigen' or 'HBsAg' includes any HBsAg antigen or fragment thereof displaying the antigenicity of HBV surface antigen. It will be understood that in addition to the 226 amino acid sequence of the HBsAg S antigen (see Tiollais et al, Nature, 317, 489 (1985) and references therein) HBsAg as herein described may, if desired, contain all or part of a pre-S sequence as described in the above references and in EP-A- 0 278 940. HBsAg as herein described can also refer to variants, for example the 'escape mutant' described in WO 91/14703.
- the HBsAg may comprise a pro tein described as SL* in European Patent Application Number 0 414 374, that is to say a protein, the amino acid sequence of which consists of parts of the amino acid sequence of the hepatitis B virus large (L) protein (ad or ay subtype), characterised in that the amino acid sequence of the protein consists of either:
- HBsAg may also refer to polypeptides described in EP 0 198 474 or EP 0 304 578. Normally the HBsAg will be in particle form. It may comprise S protein alone or may be as composite particles, for example (L*,S) wherein L* is as defined above and S denotes the S-protein of hepatitis B surface antigen.
- the HBsAg will be adsorbed on aluminium phosphate as described in WO93/24148.
- the hepatitis B antigen is HBsAg S-antigen as used in the commercial product Engerix-B (SmithKline Beecham Biologicals).
- the vaccine formulations of the present invention will contain an immunoprotective quantity of the antigens and may be prepared by conventional techniques.
- Vaccine preparation is generally described in New Trends and Developments in Vaccines, edited by Voller et al., University Park Press, Baltimore, Maryland, U.S.A. 1978.
- Encapsulation within liposomes is described, for example, by Fullerton, U.S. Patent 4,235,877.
- Conjugation of proteins to macromolecules is disclosed, for example, by Likhite, U.S. Patent 4,372,945 and by Armor et al., U.S. Patent 4,474,757.
- the vaccine compositions of the invention are preferably administered in a 0, 6 month schedule, that is to say a first dose at 0 months and a second dose at 6 months.
- the vaccine compositions of the present invention are especially appropriate for adults and are also appropriate for administration to adolescents and children.
- a vaccine composition for administration to adults which comprises: 40 ⁇ g HBsAg
- Aluminium salt (0.8mg aluminium phosphate plus 0.05mg aluminium hydroxide)
- a vaccine composition for administration to adults which comprises: 40 ⁇ g HBsAg
- Aluminium salt (0.8mg aluminium phosphate plus 0.05mg aluminium hydroxide)
- a vaccine composition for administration to adolescents and/or children which comprises:
- Aluminium salt (0.4mg aluminium phosphate plus 0.05mg aluminium hydroxide)
- a vaccine composition for administration to adolescents and/or children which comprises:
- Aluminium salt (0.4mg aluminium phosphate plus 0.05mg aluminium hydroxide)
- the immunization schedule for HAB 054 was 0,6 (i.e. doses administered at month 0 and month 6).
- the Hepatitis B serological results at months 2,6 and 7 were unexpectedly high as compared to historical results obtained in another study (HBV NF 021) in which volunteers of the same age group were included.
- Study HBV NF 021 included three groups :
- Group 1 Vaccinated with a formulation containing 40 ⁇ g of HBsAg on 0.5 ⁇ g AlPO 4 in 0.5ml volume without formol, schedule 0, 6 months (this is abbreviated in the table to NF 40 ⁇ g, 0, 6M)
- Group 2 Vaccinated with a formulation containing 20 ⁇ g of HBsAg on 0.5 ⁇ g AlPO 4 in 0.5ml volume without formol, schedule 0, 6 months (this is abbreviated in the table to NF 20 ⁇ g, 0, 6M)
- Group 3 Vaccinated with an Engerix B formulation (20 ⁇ g) using a classical 3 dose immunization schedule of 0, 1, 6 months (third row of data in Table 1 )
- HAV 1440/NF40 contains 0.85mg Al salts - 0.8 Al P0 4 20 ⁇ g formol in 1ml
- Vaccine composition comprises: 720 HAV EU / 20 ⁇ g HBs Ag 0.25mg Al Salt 40 ⁇ g formol
- Vaccine composition group 1 Two groups were used in this study. Vaccine composition group 1 :
- Vaccine composition group 2 (Twinrix TM Junior):
- Vaccine composition group 1 (Twinrix TM ). 720 HAV EU / 20 ⁇ g HBs Ag 0.45mg Al Salt 80 ⁇ g formol
- Vaccine composition group 2 1440 HAV EU / 40 ⁇ g HBs Ag
- Vaccine composition group 1 (Twinrix TM ).
- Vaccine composition group 2 (Twinrix TM Junior): 360 HAV EU / 10 ⁇ g HBs Ag 0.225mg Al Salt 40 ⁇ g formol
- Vaccine composition comprises: 720 HAV EU / 20 ⁇ g HBs Ag 0.45mg Al Salt 80 ⁇ g formol
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Priority Applications (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL99344137A PL190729B1 (pl) | 1998-05-01 | 1999-04-27 | Nowa kompozycja |
| IL13926999A IL139269A0 (en) | 1998-05-01 | 1999-04-27 | Hepatitis vaccine |
| NZ507902A NZ507902A (en) | 1998-05-01 | 1999-04-27 | Novel hepatitis vaccine composition |
| CA2331086A CA2331086C (en) | 1998-05-01 | 1999-04-27 | Hepatitis vaccine |
| DE69934108T DE69934108T2 (de) | 1998-05-01 | 1999-04-27 | Kombinierte Impfstoffe gegen Hepatitis A und Hepatitis B |
| SI9930935T SI1073462T1 (sl) | 1998-05-01 | 1999-04-27 | Kombinirano cepivo proti hepatitisu A in hepatitisu B |
| JP2000546796A JP5138843B2 (ja) | 1998-05-01 | 1999-04-27 | 新規組成物 |
| AU41379/99A AU743759B2 (en) | 1998-05-01 | 1999-04-27 | Novel composition |
| HU0101652A HU228209B1 (en) | 1998-05-01 | 1999-04-27 | New composition |
| DK99924871T DK1073462T3 (da) | 1998-05-01 | 1999-04-27 | Kombinationsvaccine mod hepatitis A og hepatitis B |
| BR9910157-2A BR9910157A (pt) | 1998-05-01 | 1999-04-27 | Composição |
| EP99924871A EP1073462B1 (en) | 1998-05-01 | 1999-04-27 | Combined vaccine against Hepatitis A and Hepatitis B |
| NO20005483A NO20005483L (no) | 1998-05-01 | 2000-10-31 | Ny sammensetning |
| HK01104910A HK1034202A1 (en) | 1998-05-01 | 2001-07-13 | Combined vaccine against hepatitis a and hepatitisb |
| US10/883,126 US7144703B2 (en) | 1998-05-01 | 2004-07-01 | Composition |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9809507.8 | 1998-05-01 | ||
| GBGB9809507.8A GB9809507D0 (en) | 1998-05-01 | 1998-05-01 | Novel composition |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09674397 A-371-Of-International | 1999-04-27 | ||
| US10/223,801 Continuation US20030049268A1 (en) | 1998-05-01 | 2002-08-20 | Novel composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1999056772A2 true WO1999056772A2 (en) | 1999-11-11 |
| WO1999056772A3 WO1999056772A3 (en) | 2000-02-03 |
Family
ID=10831426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1999/003024 WO1999056772A2 (en) | 1998-05-01 | 1999-04-27 | Hepatitis vaccine |
Country Status (29)
| Country | Link |
|---|---|
| EP (1) | EP1073462B1 (hu) |
| JP (2) | JP5138843B2 (hu) |
| KR (1) | KR100612547B1 (hu) |
| CN (1) | CN1263509C (hu) |
| AR (1) | AR016987A1 (hu) |
| AT (1) | ATE345815T1 (hu) |
| AU (1) | AU743759B2 (hu) |
| BR (1) | BR9910157A (hu) |
| CA (1) | CA2331086C (hu) |
| CO (1) | CO5050367A1 (hu) |
| CY (1) | CY1107322T1 (hu) |
| CZ (1) | CZ301232B6 (hu) |
| DE (1) | DE69934108T2 (hu) |
| DK (1) | DK1073462T3 (hu) |
| ES (1) | ES2277437T3 (hu) |
| GB (1) | GB9809507D0 (hu) |
| GC (1) | GC0000101A (hu) |
| HK (1) | HK1034202A1 (hu) |
| HU (1) | HU228209B1 (hu) |
| IL (1) | IL139269A0 (hu) |
| MY (1) | MY128929A (hu) |
| NO (1) | NO20005483L (hu) |
| NZ (1) | NZ507902A (hu) |
| PL (1) | PL190729B1 (hu) |
| PT (1) | PT1073462E (hu) |
| TR (1) | TR200003235T2 (hu) |
| TW (1) | TW553744B (hu) |
| WO (1) | WO1999056772A2 (hu) |
| ZA (1) | ZA200006118B (hu) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1862177A1 (de) * | 2006-06-01 | 2007-12-05 | Rhein Biotech Gesellschaft für neue biotechnologische Prozesse und Produkte mbH | Ein Verfahren zur Herstellung einer Impfzusammensetzung |
| EP1862176A1 (de) * | 2006-05-31 | 2007-12-05 | Rhein Biotech Gesellschaft für neue biotechnologische Prozesse und Produkte mbH | Ein Verfahren zur Herstellung einer Impfzusammensetzung |
| CN102988975A (zh) * | 2012-11-30 | 2013-03-27 | 深圳康泰生物制品股份有限公司 | 甲型、乙型肝炎联合疫苗及其制备方法 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1513555A (zh) * | 2003-07-31 | 2004-07-21 | 长春生物制品研究所 | 甲-乙型肝炎联合疫苗及其冻干制剂 |
| CN102198270B (zh) * | 2011-05-16 | 2012-06-27 | 大连汉信生物制药有限公司 | 一种含铝佐剂乙肝疫苗的制备方法 |
| KR101281098B1 (ko) * | 2011-06-30 | 2013-07-02 | 주식회사 녹십자 | Ｂ형 간염 바이러스 표면 항원상의 에피토프 및 이의 용도 |
| US9849066B2 (en) | 2013-04-24 | 2017-12-26 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
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| WO1993024148A1 (en) * | 1992-05-23 | 1993-12-09 | Smithkline Beecham Biologicals (S.A.) | Combined vaccines comprising hepatitis b surface antigen and other antigens |
| WO1996026741A1 (en) * | 1995-02-25 | 1996-09-06 | Smithkline Beeecham Biologicals S.A. | Hepatitis b vaccine |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPH0349686A (ja) * | 1989-07-11 | 1991-03-04 | Smithkline Biologicals Sa | レトロウイルスｇａｇ蛋白の真核生物細胞における発現 |
| US6372225B1 (en) * | 1996-03-23 | 2002-04-16 | The Research Foundation Of Microbial Diseases Of Osaka University | Tetanus toxin functional fragment antigen and tetanus vaccine |
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1998
- 1998-05-01 GB GBGB9809507.8A patent/GB9809507D0/en not_active Ceased
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1999
- 1999-04-27 EP EP99924871A patent/EP1073462B1/en not_active Expired - Lifetime
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- 1999-04-27 AT AT99924871T patent/ATE345815T1/de active
- 1999-04-27 PT PT99924871T patent/PT1073462E/pt unknown
- 1999-04-27 WO PCT/EP1999/003024 patent/WO1999056772A2/en active IP Right Grant
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- 1999-04-27 BR BR9910157-2A patent/BR9910157A/pt not_active Application Discontinuation
- 1999-04-27 KR KR1020007012162A patent/KR100612547B1/ko not_active IP Right Cessation
- 1999-04-27 DK DK99924871T patent/DK1073462T3/da active
- 1999-04-27 TR TR2000/03235T patent/TR200003235T2/xx unknown
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- 1999-06-29 TW TW088110991A patent/TW553744B/zh not_active IP Right Cessation
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| WO1993024148A1 (en) * | 1992-05-23 | 1993-12-09 | Smithkline Beecham Biologicals (S.A.) | Combined vaccines comprising hepatitis b surface antigen and other antigens |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1862176A1 (de) * | 2006-05-31 | 2007-12-05 | Rhein Biotech Gesellschaft für neue biotechnologische Prozesse und Produkte mbH | Ein Verfahren zur Herstellung einer Impfzusammensetzung |
| WO2007137847A1 (en) * | 2006-05-31 | 2007-12-06 | Rhein Biotech Gesellschaft für neue Biotechnologische Prozesse und Produkte mbH | Process for production of a vaccine composition |
| EP1862177A1 (de) * | 2006-06-01 | 2007-12-05 | Rhein Biotech Gesellschaft für neue biotechnologische Prozesse und Produkte mbH | Ein Verfahren zur Herstellung einer Impfzusammensetzung |
| WO2007137846A1 (en) * | 2006-06-01 | 2007-12-06 | Rhein Biotech Gesellschaft für neue Biotechnologische Prozesse und Produkte mbH | Process for production of a vaccine composition |
| CN102988975A (zh) * | 2012-11-30 | 2013-03-27 | 深圳康泰生物制品股份有限公司 | 甲型、乙型肝炎联合疫苗及其制备方法 |
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